these, only the 8-aminoquinoline derivatives (F) appeared
to be promising for further study. Even with this most
favorable derivative for functionalization, we were not able
to obtain useful yields of â-acetoxy-R-phthaloylamino acid
confirmed by single-crystal X-ray diffraction analysis (Figure
1). The diastereoselectivity of the reaction was estimated
5
8-aminoquinoline amide products under previously employed
conditions for Pd-catalyzed acetoxylation. For instance, when
N-phthaloyleucine 8-aminoquinoline amide 1 and 0.2 equiv
of Pd(OAc)
and Ac O in ClCH
t-BuOOH and 5 equiv of Ac
2
were heated with either 2 equiv of C
CH Cl at 80 °C for 12 h or 5 equiv of
O in C at 110 °C for 8 h,
6 5 2
H I(OAc)
2
2
2
2
7 8
H
none of the desired â-acetoxylated product 2 could be
detected and, in fact, only the starting material 1 was recov-
ered. These conditions have been shown to effect function-
3
f,h,j
alization at â-methyl groups in ketone O-methyloximes.
However, we were pleased to find that treatment of 1 with
0 mol % of Pd(OAc) , 5 equiv of t-BuOOH, and 5 equiv
of Ac O in benzene at 80 °C in the presence of 1.2 equiv of
Mn(OAc) gave 2 in 30% yield. This noteworthy acceleration
Figure 1. ORTEP representation of 2.
2
2
2
1
2
by H NMR analysis of the total reaction product as 20:1.
Under the same conditions as those described just above
for the transformation of 1 to 2, the alanine derivative 4a
was converted into the serine derivative 5a in 52% yield.
These conditions also resulted in the analogous conversion
with the â-phenylalanine series of 4b to 5b (63%). In the
case of reactant 4b, the reaction was completely diastereo-
selective for 5b, whereas for 4c and 4d diastereoselectivities
were on the order of 5:1 and 8:1, respectively, favoring in
each case the (3S)-diastereomers (5c and 5d). The observed
stereochemistry of the â-functionalization can be understood
in terms of a preference for forming the sterically more
favored intermediate trans-palladacycle G.
of reaction rate by Mn(II) has not previously been reported.
Although AgOAc has been found to be beneficial to certain
4
Pd(OAc)
reaction was observed when Mn(OAc)
AgOAc in the acetoxylation experiment with 1. Additional
experimentation demonstrated that Cu(OAc) and Co(OAc)
were also ineffective. With Mn(OAc) as a promoter, we
found that Oxone (2KHSO /KHSO /K SO ) (5 equiv) was
superior as an oxidant to t-BuOOH and that CH NO and
ClCH CH Cl (especially the former) served as the most
2
-catalyzed C-C couplings with aryl iodides, no
2
was replaced by
2
2
2
5
4
2
4
3
2
2
2
effective solvents for the â-acetoxylation of the R-phthaloyl-
amino acid amides investigated in the present work. Thus,
the reaction of 1 with 20 mol % of Pd(OAc)
equiv), acetic anhydride (10 equiv), and Mn(OAc)
equiv) in CH NO at 80 °C for 22 h (under air) afforded the
2
, Oxone (5
2
(1.2
3
2
crystalline (3S)-acetate 2 in 60% isolated yield along with
the (3R)-diastereomer 3 (ca. 4%). The structure of 2 was
(
3) (a) Constable, A. G.; McDonald, W. S.; Sawkins, L. C.; Shaw, B. L.
The palladacycle G, R ) i-Pr, could be generated, trapped,
and defined structurally by the reaction of 1 with p-
J. Chem. Soc., Chem. Commun. 1978, 1061. (b) Carr, K.; Sutherland, J. K.
J. Chem. Soc., Chem. Commun. 1984, 1227. (c) Baldwin, J. E.; N a´ jera, C.;
Yus, M. J. Chem. Soc., Chem. Commun. 1985, 126. (d) Jun, C.-H. Chem.
Soc. ReV. 2004, 610. (e) Jun, C.-H.; Moon, C. W.; Lee, D.-Y. Chem.-Eur.
J. 2002, 8, 2423. (f) Desai, L. V.; Hull, K. L.; Sanford, M. S. J. Am. Chem.
Soc. 2004, 126, 9542. (g) Giri, R.; Chen, X.; Yu, J.-Q. Angew. Chem., Int.
Ed. 2005, 44, 2112. (h) Giri, R.; Liang, J.; Lei, J.-G.; Li, J.-J.; Wang, D.-
H.; Naggar, I. C.; Guo, C.; Foxman, B.; Yu, J.-Q. Angew. Chem., Int. Ed.
iodoanisole (4 equiv), Pd(OAc)
2
(20 mol %), and AgOAc
(1.5 equiv, to remove HI) at 110 °C for 30 min (without
solvent) which afforded the crystalline 2S,3S-3-p-anisyl
6
derivative 6 in 95% yield. The structure of 6 was verified
by single-crystal X-ray diffraction analysis (Figure 2).5
Our results are generally supportive of the most recent
2
005, 44, 7420. (i) Dick, A. R.; Hull, K. L.; Sanford, M. S. J. Am. Chem.
Soc. 2004, 126, 2300. (j) Desai, L. V.; Malik, H. A.; Sanford, M. S. Org.
Lett. 2006, 8, 1141. (k) Zaitsev, V. G.; Shabashov, D.; Daugulis, O. J. Am.
Chem. Soc. 2005, 127, 13154. (l) Chen, X.; Hao, X.-S.; Goodhue, C. E.;
Yu, J.-Q. J. Am. Chem. Soc. 2006, 128, 6790.
3
mechanistic discussions of Pd(II)-mediated sp -C-H inser-
(
4) The use of AgOAc in Pd-catalyzed C-C bond formation with aryl
iodides has been reported; see: Shabashov, D.; Daugulis, O. Org. Lett.
005, 7, 3657.
(5) Carried out by Dr. Richard Staples; see Supporting Information for
details.
(6) For precedent, see ref 3k.
2
3392
Org. Lett., Vol. 8, No. 15, 2006